This invention relates to the treatment of patients by medicament injection and more particularly to an improvement in injection devices such as automatic injectors and syringes.
Automatic injectors are well known. Basically, an automatic injector is a device for enabling an individual to self-administer, or administer to another, a dosage of a liquid medicament. An advantage of automatic injectors is that they contain a measured dosage of a liquid medicament in a sealed sterile condition capable of storage in such condition for an extensive period of non-use, during which period immediate injection of the stored dosage may be accomplished at any time under severe emergency conditions. Another advantage of automatic injectors is that the administration of the self-contained dosage of liquid medicament is accomplished without the necessity of the user initially seeing the hypodermic needle through which the liquid medicament is injected or of manually penetrating such a visible needle into the user's or another person's tissue. Instead, an automatic injector includes a releasable energy source, typically a stressed spring assembly. A spring assembly typically includes a stressed spring, a mechanism for releasably retaining the spring in a stressed storage position, and a releasing mechanism for releasing the releasable mechanism in response to a predetermined actuating procedure.
As stated above, automatic injectors are particularly suited for use under emergency conditions. For example, many tens of millions of such automatic injectors have been manufactured and sold containing nerve gas antidotes for use under emergency chemical warfare conditions. Typical units which have been utilized for this purpose are disclosed in U.S. Pat. Nos. 2,832,339, 3,882,863, and 4,031,893. In addition, units of this type have been manufactured and used in administering antiarrhythmic medicaments under emergency conditions relating to heart attack medical situations. The use of an auto injector has also been proposed to provide other medicaments useful in treating heart attack symptoms such as clot selective thrombolytic agents (for example, tPA) and related medicaments. See, for example, U.S. Pat. Nos. 4,689,042, 4,755,169, and 4,795,433. Finally, automatic injectors have been marketed containing a dosage of epinephrine as an antidote for counteracting severe allergic reactions, as for example, to bee stings, and the like.
In all of these instances, the auto-injector is specifically structured so that in its normal operation, the needle extends into the muscle tissue of the user and a specified amount of liquid medicament stored in a cartridge within the injector is injected into the tissue of the user.
Since these injectors are to be used most often in emergency situations, it can be appreciated that such injectors must be very reliable in its administration of a medicament. These injectors must operate correctly even after being stored for an extensive period of time. At the same time, these injectors should be small enough and light enough to enable the user, who may be subject to an emergency condition, to easily carry the injector on his or her person at all times. It can also be appreciated that the injectors must be durable and be able to withstand shock from impact which can occur when the injector is continuously kept on a user's person, such as in the user's pocket or the like. This is especially the case when such injectors are carried by soldiers during times of warfare.
Heretofore, the cartridge for containing the medicament in most automatic injectors has been made from glass. This is primarily due to the fact that glass is highly stable and largely non-reactive with contained medicaments even after long periods of contact.
However, several problems exist with automatic injectors having glass cartridges. One major problem is that such cartridges must be specially made or uniquely protected in order to reduce the likelihood of breakage. For example, the cartridge might be made thicker and thus heavier. As a result, the automatic injector as a whole becomes somewhat larger, more costly, more complicated or all of the above. In addition, the injector becomes an inconvenience to an individual who must carry the injector at all times. Furthermore, even with making these provisions, the cartridge nevertheless remains subject to breakage. Such breakage can occur for numerous reasons. For example, the automatic injector may be dropped or otherwise exposed to severe mechanical shock. Another instance in which such breakage may occur is during filling of the cartridge with medicament. Oftentimes, the filling machines are limited in the speed at which such cartridges can be filled and then closed (with an elastic plunger or the like) due to the somewhat delicate nature of the glass material. Even with slower filling and assembly speeds, such glass cartridges are nevertheless subject to breakage. A further situation in which the glass cartridge may break is where the spring assembly provided for forcing an expelling plunger through the cartridge does so in an erratic fashion. Specifically, any bending of the spring may cause the spring to impact against the inner glass surface of the cartridge and cause breakage thereof. In addition, the mere compression of medicament within the glass cartridge during compressive expulsion of such medicament with the plunger may be sufficient to cause breakage of the cartridge if proper precautions are not taken. While the above-mentioned scenarios are extremely infrequent and unlikely, it can be appreciated that the emergency use of these injectors requires that such scenarios be limited to the fullest extent feasible.
Aside from breakage, two other problems exist with glass cartridges. First, they are relatively expensive to manufacture, and second, they are very difficult to manufacture with close tolerances.
Thus, there is a need for an automatic injector which has a cartridge made from a substance which is more durable, workable and/or less expensive than glass. In at least one instance metal has been used. Specifically, an automatic injector having a stainless steel cartridge is manufactured by the assignee of the present invention and sold under the registered trademark ATROPEN.RTM.. While it has also been determined that plastic might be another viable alternative, it has heretofore not been widely practical as will be discussed later.
Metal and plastic both have several advantages over glass in that it can be made both thinner and lighter while at the same time stronger than glass. Thus, the automatic injector can become more durable and more reliable. However, several problems exist with providing such metal and plastic cartridges. First, metal cartridges may react with certain (if not all) medicaments (for example, lidocaine) and thereby contaminate such medicaments. With respect to plastic, a problem exists in that plastic is not completely impervious to moisture and oxygen, and therefore not well suited to store a medicament for extended periods. Thus, while it may also be desirable to use plastic in the main body of a prefilled conventional syringe (in addition to use in automatic injectors), such use has heretofore also been rather impractical for many types of medicines.
Another problem with metal, plastic, and even glass syringe and autoinjector medicament containers, is that a plunger provided therein for expelling medicament therefrom has a tendency to adhere to the side walls thereof during extended periods of non-use. For example, it has been known that a resilient plunger sitting in contact with a metallic cartridge for a significant period of time may eventually become slightly adhered to the metallic surface of the cartridge. At the same time, it has been found that the stressed spring contained within an auto-injector weakens in strength after remaining in compression for extended periods. As a result, when the auto-injector is eventually actuated, there is a possibility that the speed with which the plunger travels through the cartridge will be reduced as a result of the friction and adhesion between the plunger and cartridge. Thus, the medicament may not be dispensed at all or will be dispensed more slowly than what might otherwise be possible. This is significant since the time interval which lapses before a full dosage of medicament is dispensed may be important to the remedial results which are obtained by administration of the medicament.
It is therefore an object of the present invention to solve the problems mentioned above. These problems can be remedied by providing an automatic injector having a metallic or plastic cartridge coated by an appropriate substance. While it has been known to treat glass and other type cartridges with silicone oil or emulsion, to reduce the coefficient of friction of the sliding plunger, such silicone is undesirable. Silicone, ideally, should not be injected into a patient. In addition, such silicone does not adequately prevent metal from reacting with the medicament contained in the cartridge and does not prevent penetration of moisture and oxygen through plastic. Moreover, while silicone can be effectively baked onto the surface of glass vials or cartridges at high temperature, it has been found that silicone is more difficult to adhere to metal or plastic to provide the same lubricating effect. Therefore, to solve these problems, the present invention contemplates providing a plastic or metallic cartridge having a polyparaxylylene coating applied to at least an inner surface thereof. When such coating is applied to metal, medicament contamination is prevented, the injector is less subject to breakage than if glass were used as a container, is more reliable and efficient in plunger operation, and is less expensive to manufacture with tighter tolerances.
When such coating is applied to plastic, all the above advantages are obtained with the additional benefits associated with the barrier effect of the coating which makes the surface of plastic resistant to moisture and oxygen transmission. From this standpoint, it is a further object of the present invention to provide a syringe having a plastic body with a polyparaxylylene coating applied to at least an inner surface thereof.
Polyparaxylylene has been found to be useful in coating various materials. For example, in Romberg et al, U.S. Pat. No. 5,000,994 it is disclosed that it is useful to coat rubber closures in order to reduce ion extraction from the rubber material into the medicament and to reduce the coefficient of friction of the surface of such rubber closures to facilitate the manufacture thereof as such rubber components may become hung up on one another or on transfer equipment. This disclosure is not concerned with using polyparaxylylene to coat a non-glass container to provide a more economic, reliable, and durable container. It should also be noted that it has been found that application of polyparaxylylene to the plunger in an automatic injector may harden the elastic surface of the plunger and may have a detrimental effect on the seal between the plunger and cartridge.
Romberg et al, U.S. Pat. No. 4,882,210, on the other hand, discloses the use of polyparaxylylene for coating a glass container in order to prevent ion extraction from the glass and increase the crush strength of the glass. The disclosure addresses the fact that during assembly with a rubber stopper, glass vials are subject to breakage. The patent suggests that providing a polyparaxylylene coating to at least one side of a glass container can increase the strength of such glass container. However, this patent fails to appreciate that polyparaxylylene can effectively be used to coat other substances, such as metal and plastic, to not only obtain compatibility of such materials with medicaments, but also allows use of other materials to effectively increase the strength of a container by several orders of magnitude over that of glass.
None of the above-mentioned references contemplates coating a metallic or plastic container for medicaments, as glass has long been the material of choice for containing medicaments. Moreover, no one has ever suggested the use of such coated container for the specialized application in automatic injectors. In addition, none of the art has attempted to utilize polyparaxylylene to coat a metallic or plastic injector cartridge so that it can more easily cooperate with a plunger to more speedily and reliably dispense a medicament from a medicament cartridge, nor has the art attempted to coat the inner surface of a plastic medicament container to reduce the permeability of such housing to oxygen and moisture. This may be due to the fact that the art related to polyparaxylylene has heretofore not concerned itself with the need to carry medicaments into harsh environments such as those environments into which an automatic injector must be taken.
Therefore, it is an object of the present invention to provide an automatic injector comprising a housing having a metallic cartridge contained therein. The cartridge has at least an inner surface thereof provided with a polyparaxylylene coating. A charge of medicament is contained within the metallic cartridge and in communication with the polyparaxylylene coating, which reduces the coefficient of friction of the inner surface of the cartridge and prevents metallic ions from being extracted from the cartridge and into the medicament. A plunger is normally disposed in a generally rearward end of the metallic cartridge, and is movable through the cartridge toward a generally forward end thereof in response to a predetermined actuating procedure. The movable plunger rearwardly confines the medicament within the metallic cartridge and is in slidable sealed relation with the polyparaxylylene coating provided on the metallic cartridge. The polyparaxylylene coating reduces the tendency of the plunger to adhere to the inner surface and reduces the time required for the plunger to travel from the generally rearward end to the generally forward end of the metallic cartridge. A needle is normally disposed within the housing and is projectable from a forward end of the housing and communicable with the medicament so that movement of the plunger through the cartridge forces the medicament through the needle and into the tissue of a user in response to the predetermined actuating procedure. In addition, a releasable energy source is releasable in response to the predetermined actuating procedure to project the needle and slidingly drive the plunger through the metallic sealed relation to expel the medicament through the needle and into the tissue of the user.
It is a further object of the present invention to provide a plastic housing for an automatic injector and/or syringe to limit permeability thereof to oxygen and moisture.
In another aspect of the present invention, it can be appreciated that certain of the aforementioned automatic injectors are provided with a metallic needle that is normally stored in contact with a medicament. Such type of injectors are disclosed in our previously granted U.S. Pat. Nos. 4,484,910, 5,085,642, and 5,092,843. An advantage of such injectors is that they have a shorter axial length than other type of injectors that have the needle normally stored in a separately provided chamber disposed forwardly of the medicament (e.g. see our previously granted U.S. Pat. No. 5,102,393). As stated previously, metal cartridges may react with certain medicaments, such as lidocaine, and thereby contaminate such medicaments. To solve the problem associated with such contamination, it is a further object of the present invention to provide an automatic injector which comprises a housing, a cartridge contained within the housing, a charge of medicament contained in the cartridge, and a needle normally disposed within the cartridge so as to be in communication with the medicament. The needle is provided with a polyparaxylylene coating for preventing ions from being extracted from the needle into the medicament. The needle is projectable from a forward end of the housing, while a plunger is normally disposed in a generally rearward end of the cartridge and movable through the cartridge in response to a predetermined actuating procedure so as to force the medicament through the needle and into the flesh of an individual. In addition, a releasable energy source is releasable in response to the predetermined actuating procedure to project the needle from the forward end of the housing and drive the plunger through the cartridge to expel the medicament through the needle and into the flesh of the individual.
These and other objects of the present invention will become more apparent during the course of the following detailed description and appended claims. The invention may be best understood with reference to the accompanying drawings wherein illustrative embodiments are shown.